Novel nicotinamide adenine dinucleotide analogues as selective inhibitors of NAD+-dependent enzymes

Three novel dinucleotide analogues of nicotinamide adenine dinucleotide (NAD+) have been synthesised from d-ribonolactone. These compounds incorporate a thiophene moiety in place of nicotinamide and are hydrolytically stable. They have been evaluated as inhibitors of adenosine diphosphate ribosyl cyclase, glutamate dehydrogenase and Sir2 acyltransferase activities. Enzyme specificity and a high level of inhibition was observed for the dehydrogenase.